Tripterygium glycoside fraction n2: Alleviation of DSS-induced colitis by modulating immune homeostasis in mice.

ABSTRACT

BACKGROUND: The Tripterygium glycosides (TG) is the main active extractive of Tripterygium wilfordii Hook F and is widely used in clinical practice to treat inflammatory diseases (including inflammatory bowel disease). However, due to its severe toxicity, TG is restricted to the treatment of many diseases. Therefore, it is necessary to study a new method to obtain the attenuated and synergistic extracts from TG. PURPOSE: Tripterygium glycosides-n2 (TG-n2) was obtained from TG by a new preparation method. In this study, we aimed to investigate the difference in the chemical compositions between TG and TG-n2, further explored its toxicity and therapeutic effects on DSS-induced colitis in mice. METHODS: The major chemical compositions of TG and TG-n2 were analyzed by ultra-performance liquid chromatography (UPLC). Subsequently, acute toxicity test was applied to evaluate the toxicity difference between TG and TG-n2. Dextran sulfate sodium (DSS)-induced acute colitis model was used to explore the therapeutic effect of TG and TG-n2 and their potential mechanisms of action. RESULTS: We found that the chemical compositions of TG-n2 is different from TG. The main difference is the ratio of triptriolide (T11) / triptolide (T9). Acute toxicity test proved that TG-n2 was less toxic than TG. Base on this, further studies showed that TG-n2 has a similar therapeutic effect as compared to TG on attenuating the symptoms of colitis, such as diarrhea, bloody stools, body weight loss, colonic atrophy, histopathological changes, inhibiting cytokines secretion and reducing absolute lymph number. In addition, TG and TG-n2 can increase the apoptosis of T lymphocyte in vivo. Further investigated showed that TG and TG-n2 could increase the expressions of Bax and p62 on CD3-positive T cells. CONCLUSION: This study showed that oral administration of TG-n2 is safer than TG. Moreover, the attenuated TG-n2 has the similar therapeutic effect on treating experimental colitis in mice when compared to TG. Its mechanism may be related to activating the expression of Bax in T cells and inducing T cells autophagy to regulate the survival of T lymphocytes in colitis mice, thus reducing inflammation in colon.